The role of terminal tyrosine residues in the formation of tripeptide nanotubes: a crystallographic insight

Terminally protected acyclic tripeptides containing tyrosine residues at both termini self-assemble into nanotubes in crystals through various non-covalent interactions including intermolecular hydrogen bonds. The nanotube has an average internal diameter of 5 Å (0.5 nm) and the tubular ensemble is developed through the hydrogen-bonded phenolic-OH side chains of tyrosine (Tyr) residues [Org. Lett.2004, 6, 4463]. We have synthesized and studied several tripeptides 3-6 to probe the role of tyrosine residues in nanotube structure formation. These peptides either have only one Tyr residue at N- or C-termini or they have one or two terminally located phenylalanine (Phe) residues. These tripeptides failed to form any kind of nanotubular structure in the solid state. Single crystal X-ray diffraction studies of these peptides 3-6 clearly demonstrate that substitution of any one of the terminal Tyr residues in the Boc-Tyr-X-Tyr-OMe (X=Val or Ile) sequence disrupts the formation of the nanotubular structure indicating that the presence of two terminally located Tyr residues is vital for nanotube formation.     

Molecular and crystal structure of quinoline-2-aldehyde thiosemicarbazone

The molecular and crystal structure of quinoline-2-aldehyde thiosemicarbazone is determined. The thiosemicarbazide fragment has cis-arrangement of terminal nitrogen atoms relative to the central N-C bond. The structure is based on a centrosymmetric dimer formed by hydrogen bonds between NH groups and sulfur atoms of thiosemicarbazide fragments of the neighboring molecules. In the crystal, the dimers are joined with each other through a system of hydrogen bonds and intermolecular π-π interactions.     

Diphenylalanine Motif Drives Self-Assembling in Hybrid PNA-Peptide Conjugates

Peptides and nucleic acids can self-assemble to give supramolecular structures that find application in different fields, ranging from the delivery of drugs to the obtainment of materials endowed with optical properties. Forces that stabilize the “suprastructures” typically are hydrogen bonds or aromatic interactions; in case of nucleic acids, Watson-Crick pairing drives self-assembly while, in case of peptides, backbone hydrogen bonds and interactions between aromatic side chains trigger the formation of structures, such as nanotubes or ribbons. Molecules containing both aromatic peptides and nucleic acids could in principle exploit different forces to self-assemble. In this work we meant to investigate the self-assembly of mixed systems, with the aim to understand which forces play a major role and determine formation/structure of aggregates. We therefore synthesized conjugates of the peptide FF to the peptide nucleic acid dimer “gc” and characterized their aggregates by different spectroscopic techniques, including NMR, CD and fluorescence.     

Design of Amphiphilic Peptide Geometry towards Biomimetic Self‐Assembly of Chiral Mesoporous Silica

In nature, diatoms and sponges are exquisite examples of well‐defined structures produced by silica biomineralisation, in which proteins play an important role. However, the artificial peptide templating route for the silica mesostructure remains a formidable and unsolved challenge. Herein, we report our effort on the design of amphiphilic peptides for synthesising a highly ordered two‐dimensional (2D)‐hexagonal and lamellar chiral silica mesostructure using trimethoxysilylpropyl‐N,N,N‐trimethylammonium chloride as the co‐structure directing agent (CSDA). The geometry of the peptide was designed by adding proline residues into the hydrophobic chain of the peptide to break the β‐sheet conformation by weakening the intermolecular hydrogen bonds; this led to the mesophase transformation from the most general lamellar structure to the 2D hexagonal P6mm mesostructure by increasing the amphiphilic molecules packing parameter g. Enantiomerically pure chiral mesostructures were formed thanks to the intrinsic chirality and relatively strong intermolecular hydrogen bonds of peptides.     

High‐Resolution Rotational Spectroscopy Study of the Smallest Sugar Dimer: Interplay of Hydrogen Bonds in the Glycolaldehyde Dimer

Molecular recognition of carbohydrates plays an important role in nature. The aggregation of the smallest sugar, glycolaldehyde, was studied in a conformer‐selective manner using high‐resolution rotational spectroscopy. Two different dimer structures were observed. The most stable conformer reveals C₂‐symmetry by forming two intermolecular hydrogen bonds, giving up the strong intramolecular hydrogen bonds of the monomers and thus showing high hydrogen bond selectivity. By analyzing the spectra of the ¹³C and ¹⁸O isotopologues of the dimer in natural abundance, we could precisely determine the heavy backbone structure of the dimer. Comparison to the monomer structure and the complex with water provides insight into intermolecular interactions. Despite hydrogen bonding being the dominant interaction, precise predictions from quantum‐chemical calculations highly rely on the consideration of dispersion.     

Synthesis and Crystal Structure of N-Benzyl-N＇-（2-pyridyl）urea and Its Mononuclear Cu（Ⅱ） Complex

A new ligand of N-benzyl-N＇-（2-pyridyl）urea L and its self-assembly product with CuCl2, [Cu（Ⅱ）LCl2]∞ 1, have been synthesized and structurally characterized by IR, 1H NMR and single-crystal X-ray diffraction analysis. In the structure of L, the urea groups adopt Z,E conformation to form dimers through intermolecular hydrogen bonds; while in complex 1, it assumes Z,Z conformation to fit for the coordination sphere of the Cu（Ⅱ） ions. The coordinated units are connected through intermolecular N-H...Cl hydrogen bonds to form an extended 2D framework. Finally, a 3D structure is obtained via π-π stacking interactions between pyridyl rings     

Synthesis and Crystal Structure of N-Benzyl-N'-(2-pyridyl)urea and Its Mononuclear Cu(II) Complex

A new ligand of N-benzyl-N'-(2-pyridyl)urea L and its self-assembly product with CuCl2, [Cu(II)LCl2]∞ 1, have been synthesized and structurally characterized by IR, 1H NMR and single-crystal X-ray diffraction analysis. In the structure of L, the urea groups adopt Z,E conformation to form dimers through intermolecular hydrogen bonds; while in complex 1, it assumes Z,Z conformation to fit for the coordination sphere of the Cu(II) ions. The coordinated units are connected through intermolecular N-H…Cl hydrogen bonds to form an extended 2D framework. Finally, a 3D structure is obtained via π-π stacking interactions between pyridyl rings.     

A helical, aromatic, peptide nanotube

[Structure: see text] The self-assembly in the crystal state of the terminally protected, linear dipeptide Boc-(S,S)c3diPhe-(R,R)c3diPhe-NHiPr (1) through intermolecular hydrogen bonds leads to the formation of a supramolecular helix of large diameter (18 A), internally decorated with phenyl rings. As a result, a hollow helical channel large enough to accommodate guest molecules is observed. This supramolecular structure differs from previous examples of peptide nanotubes. Compound 1 incorporates a highly restricted cyclopropane phenylalanine analogue (c3diPhe) with remarkable conformational properties.     

Structure and matrix isolation infrared spectrum of formyl fluoride dimer: blue-shift of the C-H stretching frequency

Infrared spectroscopy (IR) of formyl fluoride (HCOF) dimer is studied in low-temperature argon and krypton matrixes. New IR absorptions, ca. 17 cm(-1) blue shifted from the monomer C-H stretching fundamental, are assigned to the HCOF dimer. The MP2/6-311++G calculations were utilized to define structures and harmonic frequencies of various HCOF dimers. Among the four optimized structures, the dimer having two C-H...O hydrogen bonds possesses strongest intermolecular bonding. The calculated harmonic frequencies of this dimer structure are shifted from the monomer similarly as observed in the experiment. Thus, we suggest that the experimentally observed blue shifted C-H bands belong to the dimer with two C-H...O hydrogen bonds. This observation includes the HCOF dimer to the class of hydrogen bonded complexes showing blue shift in their vibrational energies.     

Dimerization of the keto tautomer of acetohydroxamic acid-infrared matrix isolation and theoretical study

Dimerization of the keto tautomer of acetohydroxamic acid has been studied using FTIR matrix isolation spectroscopy and DFT(B3LYP)/6-31+G(d,p) calculations. Analysis of CH3CONHOH/Ar matrix spectra indicates formation of two dimers in which two intramolecular CO...HON bonds within two interacting acetohydroxamic acid molecules are retained. A chain dimer I is stabilized by the intermolecular CO...HN hydrogen bond, whereas the cyclic dimer II is stabilized by two intermolecular NH...O(H)N bonds. Twelve vibrations were identified for dimer I and six vibrations for dimer II; the observed frequency shifts show a good agreement with the calculated ones for the structures I and II. Both dimers have comparable binding energies (DeltaE(ZPE)(CP)I, II=-7.02, -6.34 kcal mol-1) being less stable than calculated structures III and IV (DeltaE(ZPE)(CP)III, IV=-9.50, -8.87 kcal mol-1) in which one or two intramolecular hydrogen bonds are disrupted. In the most stable 10-membered cyclic dimer III, two intermolecular CO...HON hydrogen bonds are formed at expense of intramolecular hydrogen bonds of the same type. The formation of the less stable (AHA)2 dimers in the studied matrixes indicates that the formation of (AHA)2 is kinetically and not thermodynamically controlled.     

Synthesis,characterization, and X-ray crystal structures of zinc(II) complexes with schiff bases 2-[(2-isopropylaminoethylimino)methyl]-5-methoxyphenol and N,N-dimethyl-N′-(1-pyridin-2-ylethylidene)ethane-1,2-diamine

Two new zinc(II) complexes, [ZnBr₂L¹] (I) and [ZnBr₂L²] (II), where L¹ is 2-[(2-isopropylaminoethylimino)methyl]-5-methoxyphenol and L² is N,N-dimethyl-N′-(1-pyridin-2-yl-ethylidene)ethane-1,2-diamine, were prepared and characterized using elemental analysis, FT-IR spectroscopy, and X-ray single-crystal diffraction. In complex I, the Zn(II) atom is coordinated by one phenolic O and one imino N atoms of L¹ and two Br atoms, forming a tetrahedral coordination geometry. In complex II, the Zn(II) atom is in a trigonal bipyramidal coordination geometry with the equatorial plane formed by the imino N atom of L² and two Br atoms and with the two axial positions occupied by one pyridine N and one amino N atoms of L². In the crystal structure of I, the mononuclear zinc complex molecules are linked through intermolecular N-H…O and N-H…Br hydrogen bonds, forming chains running along the y axis. The chains are further linked via intermolecular C-H…Br hydrogen bonds. In the crystal structure of II, the mononuclear zinc complex molecules are linked through intermolecular C-H…Br hydrogen bonds, forming a 3D network.     

Fibril Structure Demonstrates the Role of Iodine Labelling on a Pentapeptide Self-Assembly

Iodination has long been employed as a successful labelling strategy to gain structural insights into proteins and other biomolecules via several techniques, including Small Angle X-ray Scattering, Inductively Coupled Plasma Mass Spectrometer (ICP-MS), and single-crystal crystallography. However, when dealing with smaller biomolecular systems, interactions driven by iodine may significantly alter their self-assembly behaviour. The engineering of amyloidogenic peptides for the development of ordered nanomaterials has greatly benefitted from this possibility. Still, to date, iodination has exclusively been applied to aromatic residues. In this work, an aliphatic bis-iodinated amino acid was synthesized and included into a custom pentapeptide, which showed enhanced fibrillogenic behaviour. Peptide single crystal X-ray structure and powder X-ray diffraction on its dried water solution demonstrated the key role of iodine atoms in promoting intermolecular interactions that drive the peptide self-assembly into amyloid fibrils. These findings enlarge the library of halogenated moieties available for directing and engineering the self-assembly of amyloidogenic peptides.     

Syntheses, characterizations and crystal structures of new organoantimony(V) complexes with heterocyclic (S, N) ligand

Eight new organoantimony(V) complexes with 1-phenyl-1H-tetrazole-5-thiol [L¹H] and 2,5-dimercapto-4-phenyl-1,3,4-thiodiazole [L²H] of the type R_nSbL_5 − n (L = L¹: n = 4, R = n-Bu 1, Ph 2, n = 3, R = Me 3, Ph 4; L = L²: n = 4, R = n-Bu 5, Ph 6, n = 3, R = Me 7, Ph 8) have been synthesized. All the complexes 1-8 have been characterized by elemental, FT-IR, ¹H and ¹³C NMR analyses. Among them complexes 2, 6 and 8 have also been confirmed by X-ray crystallography. The structure analyses show that the antimony atoms in complexes 2 and 6 display a trigonal bipyramid geometry, while it displays a distorted capped trigonal prism in complex 8 with two intramolecular Sb?N weak interactions. Furthermore, the supramolecular structure of 2 has been found to consist of one-dimensional linear molecular chain built up by intermolecular C-H?N weak hydrogen bonds, while a macrocyclic dimer has been found in complex 6 linked by intermolecular C-H?S weak hydrogen bonds with head-to-tail arrangement. Interestingly, one-dimensional helical chain is recognized in complex 8, which is connected by intermolecular C-H?S weak hydrogen bonds.     

Some features of the crystal and molecular structure of N-(1,2,4-triazol-5-yl)benzamidine and its hydrochloride

The crystal and molecular structures of N-(1,2,4-triazol-5-yl)benzamidine (1) and its hydrochloride (2) were determined by x-ray crystallography. In compound 1 both independent molecules are Z isomers of the anidine substituted in the imino group and 5-substituted 1H-1,2,4-triazoles. In the crystal the molecules of compound 1 are linked into a stable dimer by intermolecular hydrogen bonds. An undissociated HCl molecule was unexpectedly found in the structure of compound 2, while the structure of the base corresponded to the Z isomer of the amidine substituted in the amino group and to 2H-1,2,4-triazole substituted at position 5. The structures of compounds 1 and 2 are stabilized by an intramolecular hydrogen bond. The HCl molecule participates in the formation of intermolecular hydrogen bonds in compound 2.N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, 117913 Moscow. Translated fromIzvestiya Akademii Nauk, Seriya Khimicheskaya, No. 6, pp. 1380–1386, June, 1992.     

Molecular dynamics simulation of thermal unfolding of Thermatoga maritima DHFR

Molecular dynamics simulations of the temperature-induced unfolding reaction of native dimeric dihydrofolate reductase from the hyperthermophile Thermatoga maritima (TmDHFR) and the experimentally inaccessible TmDHFR monomer were carried out at 400 K, 450 K and 500 K. The results revealed that the unfolding of TmDHFR subunits followed a similar path to that of the monomeric DHFR from the mesophile E. coli (EcDHFR). An initial collapse of the adenosine-binding domain (ABD) was followed by the loss of the N-terminal and loop domains (NDLD). Interestingly, the elements of the secondary structure of the isolated TmDHFR monomer were maintained for significantly longer periods of time for the hyperthermophilic enzyme, suggesting that subunit stability contributes to the enhanced resistance of TmDHFR to temperature-induced unfolding. The interactions between the subunits of the TmDHFR dimer led to a stabilisation of the NDLD. The hydrogen bonds between residues 140-143 in betaG of one subunit and residues 125-127 in betaF of the other subunit were retained for significant parts of the simulations at all temperatures. These intermolecular hydrogen bonds were lost after the unfolding of the individual subunits. The high stability of the dimer mediated by strong intersubunit contacts together with an intrinsically enhanced stability of the subunits compared to EcDHFR provides a molecular rational for the higher stability of the thermophilic enzyme. The computed unfolding pathways suggest that the partly folded dimer may be a genuine folding intermediate.     

Intramolecular ditryptophan crosslinks enforce two types of antiparallel beta structures.

BACKGROUND: Two types of biaryl crosslinks can be formed with natural protein sidechains: ditryptophan and dityrosine. Biaryl crosslinks have the same topology as disulfide crosslinks, yet little is known about their effect on local peptide structure. RESULTS: Three ditryptophan-linked peptide dimers based on the sequence Ac-Leu-Trp-Ala-COX were prepared. The tripeptide dimer with -CONH(2) termini was too insoluble to study, but the tripeptide dimer with -COOMe termini crystallized from methanol/chloroform as an antiparallel beta-sheet. The tripeptide dimer with a -CONMe(2) termini adopted a slipped antiparallel beta structure in methanol/chloroform. CONCLUSIONS: These results suggest that intermolecular ditryptophan crosslinks that join the middle of peptide chains can confer a preference for antiparallel beta-sheet structure. The effect is most dramatic when both the inside and outside edges of the dimer can form hydrogen bonds as in the crystal structure of dimer 3b.     

Mechanochemical Mediated Coexistence of B←N Coordination and Hydrogen Bonding

Mechanochemistry afforded a photoactive cocrystal via coexisting (B)O−H⋅⋅⋅N hydrogen bonds and B←N coordination. Specifically, solvent-free mechanochemical ball mill grinding and liquid-assisted grinding of a boronic acid and an alkene resulted in mixtures of hydrogen-bonded and coordinated complexes akin to mixtures of noncovalent complexes that can be obtained in solution in equilibria processes. The alkenes of the hydrogen-bonded assembly undergo an intermolecular [2+2] photodimerization in quantitative conversion, effectively reporting the outcome of the self-assembly processes. Our results suggest that interplay involving noncovalent bonds subjected to mechanochemical conditions can lead to functional solids where, in the current case, the structure composed of the weaker hydrogen bonding interactions predominates.     

Four different types of hydrogen bonds observed in 1,2-bis(N-benzenesulfonylamino)benzenes due to conformational properties of the sulfonamide moiety

The crystal structures of 1,2-bis(N-benzenesulfonylamino)benzenes with secondary and/or tertiary sulfonamide groups were determined by X-ray crystallographic analysis. Every Ar-sulfonamide group existed in synclinal conformation in the crystals even though it was secondary or tertiary. Each compound showed different types of hydrogen bonds in the crystal structure. 1,2-Bis(N-benzenesulfonylamino)benzene (1) formed two double hydrogen bonds connected to the next molecules, 1-(N-benzenesulfonylamino)-2-(N-benzenesulfonyl-N-methylamino)benzene (2) contained double hydrogen bond involved by both the sulfonamide moieties, 1,2-bis(N-4-toluenesulfonylamino)benzene (3) had both intra- and intermolecular hydrogen bonds, and 1-(N-methyl-N-4-toluenesulfonylamino)-2-(N-4-toluenesulfonylamino)benzene (4) had one double hydrogen bond involved by only one sulfonamide moiety. Sulfonamides 1 and 3 formed infinite arrays of the molecules, and sulfonamides 2 and 4 formed racemic dimer of their conformational enantiomers via the hydrogen bonds.     

X‐Ray Crystal Structure of a Second‐Generation Peptide Dendrimer in Complex with Pseudomonas aeruginosa Lectin LecB

Dendrimers are regularly branched molecular trees which are notoriously difficult to crystallize. Herein we report the crystal structure of a C‐fucosylated second generation peptide dendrimer as complex with lectin LecB in which the only dendrimer‐lectin contact is the LecB bound glycoside (PDB 6S5S). In contrast to a previously reported crystal structure of a first‐generation peptide dendrimer as LecB complex in which the dendrimer formed trimers connected by intermolecular β‐sheets (PDB 5D2A), the present structure features a globular monomeric state held together by intramolecular backbone hydrogen bonds and assembled into a non‐covalent dimer stabilized by hydrophobic contacts between leucine side‐chains and proline‐phenylalanine CH‐π stacking interactions. Molecular dynamics and circular dichroism studies suggest that this crystal structure resembles the structure of the peptide dendrimer in solution. Structures of a partially resolved dendrimer (PDB 6S5R) and of C‐fucosylated disulfide bridged peptide dimers connecting different LecB tetramers are also reported (PDB 6S7G, PDB 6S5P).     

Structural characterization of methionine and leucine enkephalins by hydrogen/deuterium exchange and electrospray ionization tandem mass spectrometry

Conformational changes in two endogenous opioid active pentapeptides methionine enkephalin (Met-enk) and leucine enkephalin (Leu-enk) induced by trifluoroethanol (TFE) were identified using hydrogen/deuterium exchange (HDX), coupled with electrospray ionization (ESI) mass spectrometry. The exchange features in individual amino acid residues were characterized by acquiring tandem mass spectra of the deuterated peptides. The exact identity of the labile hydrogens involved in HDX reveals that the monomer forms of both peptides adopt an unfolded conformation in aqueous solvent, but prefer the 5-->2 beta-turn secondary structure under the membrane-mimetic environment. The ESI mass spectra of Met-enk and Leu-enk also reveal that the dimer structure of these peptides coexists with the monomer conformation. The extent of the dimer structure is dependent on the peptide concentration and nature of the solvent. The non-polar solvents facilitate the dimer formation.